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The neurodegenerative disorder Alzheimer's disease is characterised by the formation of β-amyloid plaques and neurofibrillary tangles in the brain parenchyma, which cause synapse and neuronal loss. This leads to clinical symptoms, such as progressive memory deficits. Clinically, these pathological changes can be detected in the cerebrospinal fluid and with brain imaging, although reliable blood tests for plaque and tangle pathologies remain to be developed. Plaques and tangles often co-exist with other brain pathologies, including aggregates of transactive response DNA-binding protein 43 and Lewy bodies, but the extent to which these contribute to the severity of Alzheimer's disease is currently unknown. In this ‘At a glance’ article and poster, we summarise the molecular biomarkers that are being developed to detect Alzheimer's disease and its related pathologies. We also highlight the biomarkers that are currently in clinical use and include a critical appraisal of the challenges associated with applying these biomarkers for diagnostic and prognostic purposes of Alzheimer's disease and related neurodegenerative disorders, also in their prodromal clinical phases.

Synaptic degeneration and neuronal loss are early events in Alzheimer’s disease (AD), occurring long before symptom onset, thus making synaptic biomarkers relevant for enabling early diagnosis. The postsynaptic protein neurogranin (Ng) is a cerebrospinal fluid (CSF) biomarker for AD, also in the prodromal phase. Here we tested the hypothesis that during AD neurodegeneration, processing of full-length Ng into endogenous peptides in the brain is increased. We characterized Ng in post-mortem brain tissue and investigated the levels of endogenous Ng peptides in relation to full-length protein in brain tissue of patients with sporadic (sAD) and familial Alzheimer’s disease (fAD), healthy controls and individuals who were cognitively unaffected but amyloid-positive (CU-AP) in two different brain regions. Brain tissue from parietal cortex [sAD (n = 10) and age-matched controls (n = 10)] and temporal cortex [sAD (n = 9), fAD (n = 10), CU-AP (n = 13) and controls (n = 9)] were included and all the samples were analyzed by three different methods. Using high-resolution mass spectrometry, 39 endogenous Ng peptides were identified while full-length Ng was found to be modified including disulfide bridges or glutathione. In sAD parietal cortex, the ratio of peptide-to-total full-length Ng was significantly increased for eight endogenous Ng peptides compared to controls. In the temporal cortex, several of the peptide-to-total full-length Ng ratios were increased in both sAD and fAD cases compared to controls and CU-AP. This finding was confirmed by western blot, which mainly detects full-length Ng, and enzyme-linked immunosorbent assay, most likely detecting a mix of peptides and full-length Ng. In addition, Ng was significantly associated with the degree of amyloid and tau pathology. These results suggest that processing of Ng into peptides is increased in AD brain tissue, which may reflect the ongoing synaptic degeneration, and which is also mirrored as increased levels of Ng peptides in CSF.

The development and use of experimental models using lymphatic cannulation techniques have been hampered by the lack of high-quality colour imaging of lymphatic vessels in situ. Most descriptions of lymphatic anatomy in sheep have historically depended on schematic diagrams due to limitations in the ability to publish colour images of the lymphatic vessels with decent resolution. The aim of this work was to encourage more widespread use of the ovine cannulation model by providing clear photographic images identifying the location and anatomical layout of some major lymphatic ducts and their in situ relationship to surrounding tissues. The cadavers of the sheep were collected after they had been euthanized at the end of animal trials not associated with this study. The lymphatics were dissected and exposed to show their appearance in the surrounding tissues and their relationship to other organs. Patent Blue was used to locate lymphatic vessels in exploratory preparations. However, in order to present the natural appearance of the vessels, we used minimal dissection and dye was not used for the photographed examples. Instead, we have indicated the course of the vessels with lines where their position is less clear. In this paper, we have used sheep specimens as examples to show characteristic images of lymphatic vessels. The images of in situ lymphatics and lymph nodes combined with schematic summaries provide a concise illustration of the lymphatic drainage scheme in sheep.

Abstract Multiple system atrophy (MSA) is an adult-onset neurodegenerative disease characterized by aggregation of α-synuclein in oligodendrocytes to form glial cytoplasmic inclusions. According to the distribution of neurodegeneration, MSA is subtyped as striatonigral degeneration (SND), olivopontocerebellar atrophy (OPCA), or as combination of these 2 (mixed MSA). In the current study, we aimed to investigate regional microglial populations and gene expression in the 3 different MSA subtypes. Microscopy with microglial marker Iba-1 combined with either proinflammatory marker CD68 or anti-inflammatory marker Arginase-1 was analyzed in control, SND, and OPCA cases (n = 5) using paraffin embedded sections. Western immunoblotting and cytokine array were used to determine protein expression in MSA and control brain regions. Gene expression was investigated using the NanoString nCounter Human Inflammation panel v2 mRNA Expression Assay. Analysis of neuropathological subtypes of MSA demonstrated a significant increase in microglia in the substantia nigra of OPCA cases. There was no difference in the microglial activation state in any region. Cytokine expression in MSA was comparable with controls. Decreased expression of CX3CL1 precursor protein and significantly greater CX3CR1 protein was found in MSA. NanoString analysis revealed the >2-fold greater expression of ARG1, MASP1, NOX4, PTGDR2, and C6 in MSA.

(1) Background: In the face of persistent and chronically weak labour markets, Atlantic Canada has become increasingly dependent on mobile oil work in Northern Alberta for employment and income. In the regions, most intensely engaged in this form of employment, mobile oil work has largely replaced the dominant industries of the previous century. This geographic shift in Canadian investment and production has created uneven labour markets, with high demand for labour in the Northern Alberta and high unemployment in de-industrialized communities in Atlantic Canada. (2) Methods: There is little quantitative evidence on the flows of mobile workers from the East to the West and the impact of this movement on the Atlantic Canadian economy. Data for this paper were obtained through a special arrangement with Statistics Canada in the fall of 2015 and winter of 2016, from the Canadian Employer–Employee Dynamics Database (CEEDD). (3) Results: Analysis of CEEDD revealed that the oil and gas industry of Northern Alberta has a significant impact on the economies of Atlantic Canada with an increasing dependence for interprovincial workers. (4) Conclusions: To the extent that mobile work has served as a replacement for traditional industries, mobile work is re-structuring the social and economic makeup of Atlantic Canadian communities. The more reliant Atlantic Canadian communities become on oil-related mobile work, the more precarious their economies will become as global markets for oil and gas change and targeted actions on climate change increase.

In the majority of affected brain regions the pathological hallmarks of Alzheimer’s disease (AD) are β-amyloid (Aβ) deposits in the form of diffuse and neuritic plaques, tau pathology in the form of neurofibrillary tangles, neuropil threads and plaque-associated abnormal neurites in combination with an inflammatory response. However, the anatomical area of the presubiculum, is characterised by the presence of a single large evenly distributed ‘lake-like’ Aβ deposit with minimal tau deposition or accumulation of inflammatory markers. Post-mortem brain samples from sporadic AD (SAD) and familial AD (FAD) and two hereditary cerebral amyloid diseases, familial British dementia (FBD) and familial Danish dementia (FDD) were used to compare the morphology of the extracellular proteins deposited in the presubiculum compared to the entorhinal cortex. The level of tau pathology and the extent of microglial activation were quantitated in the two brain regions in SAD and FAD. Frozen tissue was used to investigate the Aβ species and proteomic differences between the two regions. Consistent with our previous investigations of FBD and FDD cases we were able to establish that the ‘lake-like’ pre-amyloid deposits of the presubiculum were not a unique feature of AD but they also found two non-Aβ amyloidosis. Comparing the presubiculum to the entorhinal cortex the number of neurofibrillary tangles and tau load were significantly reduced; there was a reduction in microglial activation; there were differences in the Aβ profiles and the investigation of the whole proteome showed significant changes in different protein pathways. In summary, understanding why the presubiculum has a different morphological appearance, biochemical and proteomic makeup compared to surrounding brain regions severely affected by neurodegeneration could lead us to understanding protective mechanisms in neurodegenerative diseases.

Background To collect lymph draining the lungs provides a useful strategy for tracing pulmonary microvascular fluid and protein biology. A methodology that allows for in vivo sampling of efferent pulmonary lymph in real-time in sheep by cannulating the thoracic duct without entering the thoracic cavity was previously established. To develop a similar thoracic duct cannulation model without thoracotomy in pigs, we investigated the anatomy of the left cervico-thoracic regions of 15 Large White (Yorkshire or Yorkshire-dominated) piglets (aged 4–7 weeks). Results The thoracic duct, together with the left tracheal trunk, joined the cardiovascular system (the ampulla of the thoracic duct) at a site located craniomedial to the first rib on the left in 80 % (12/15) of the piglets. Conclusions As the location of the ampulla of the thoracic duct was consistent in most of the piglets, Large White piglets appear to be suitable for the development of a thoracic duct cannulation model without thoracotomy. The anatomical findings in this study will enable the development of further surgical procedures for cannulating the thoracic duct without thoracotomy, with minimal damage to local tissue, and without transecting any major blood vessels, nerves or muscle bellies. The establishment of a thoracic duct cannulation model for collecting in vivo , in situ efferent lymph, including pulmonary lymph, in pigs without entering the thoracic cavity would be invaluable for many immunological studies, studies on pulmonary immune responses in particular.

A growing number of states have modified constitutionally determined presidential term limits or adopted a flexible interpretation of relevant constitutional provisions to allow incumbent leaders additional terms in the highest office. This article investigates African Union (AU) responses to attempts to overturn or weaken term limits on executive power, one of the most tenacious constitutional trends in Africa. Inspired by the AU's well-established discourse on “unconstitutional changes of government” under the African Charter on Democracy, Elections and Governance, the article frames the manipulation of presidential term limits as “undemocratic changes of the constitution”. From this perspective it argues for a more active role for the AU in monitoring and enforcing constitutionalism and respect for democratic standards by member states when they amend their constitution. It concludes with a tentative set of principles to guide processes of constitutional change in Africa.

Objective The purpose of this review was to synthesize published literature describing integrated care education available to general psychiatry residents in the United States (US) in order to better understand curricular models and summarize curriculum barriers and facilitators. Methods The authors searched electronic databases for articles describing integrated care education for general psychiatry residents. Minimum inclusion criteria were focus on an ambulatory integrated care curriculum, description of the study population and training program, publication in English, and program location in the US. Data extracted included trainee, faculty, or collaborator evaluations, educational model, level of care integration, and barriers or facilitators to implementation. Results The literature search identified 18 articles describing curricula at 26 residency programs for inclusion. Most programs offered clinical and didactic curricula to advanced trainees across a variety of care integration levels. Common barriers included fiscal vulnerability and difficulties identifying team members or clarifying team member roles. Common facilitators included institutional and interdepartmental support, dedicated space, and faculty supervision. No statistical analysis was able to be performed due to study heterogeneity. Conclusions This review found a relatively small number of articles written about integrated care education for psychiatry residents. Resident evaluation suggests this training is valuable regardless of curriculum structure, training years, or level of care integration. Dedicated funding, staff, and space were crucial for successful curricula. This review highlights a need for more rigorous research characterizing and evaluating integrated care education.

The development and use of experimental models using lymphatic cannulation techniques have been hampered by the lack of high-quality colour imaging of lymphatic vessels in situ. Most descriptions of lymphatic anatomy in sheep have historically depended on schematic diagrams due to limitations in the ability to publish colour images of the lymphatic vessels with decent resolution. The aim of this work was to encourage more widespread use of the ovine cannulation model by providing clear photographic images identifying the location and anatomical layout of some major lymphatic ducts and their in situ relationship to surrounding tissues. The cadavers of the sheep were collected after they had been euthanized at the end of animal trials not associated with this study. The lymphatics were dissected and exposed to show their appearance in the surrounding tissues and their relationship to other organs. Patent Blue was used to locate lymphatic vessels in exploratory preparations. However, in order to present the natural appearance of the vessels, we used minimal dissection and dye was not used for the photographed examples. Instead, we have indicated the course of the vessels with lines where their position is less clear. In this paper, we have used sheep specimens as examples to show characteristic images of lymphatic vessels. The images of in situ lymphatics and lymph nodes combined with schematic summaries provide a concise illustration of the lymphatic drainage scheme in sheep.